Factors influencing T-cell turnover in HIV-1-seropositive patients
Factors influencing T-cell turnover in HIV-1-seropositive patients
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DOI：
10.1172/jci8647
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发表时间：
2000-03-01
影响因子：
15.9
通讯作者：
Hellerstein, M
中科院分区：
文献类型：
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作者：
McCune, JM;Hanley, MB;Hellerstein, M
HIV-1 疾病与 T 细胞产生、破坏和分布的病理影响有关。使用氘代 (2H) 葡萄糖方法进行内源标记，我们分析了影响未感染和感染 HIV-1 的人类 T 细胞更新的宿主因素。在未经治疗的 HIV-1 疾病中，循环 T 细胞的平均半衰期缩短，但细胞产量却没有补偿性增加。在开始高效抗逆转录病毒治疗（HAART）后12周内，循环T细胞的绝对生产率增加，并且正常半衰期和生产率在12-36个月内恢复。患者间绝对更新程度的异质性与每个 CD4+ 和 CD8+ 群体中初始 T 细胞和记忆/效应表型 T 细胞的相对比例相关。幼稚表型 T 细胞的半衰期为 116-365 天（每天的分数替换率为 0.19-0.60%），而记忆/效应表型 T 细胞的半衰期持续为 22-79 天（每天的分数替换率为 0.87-3.14%）。通过计算机断层扫描评估，在胸腺组织丰富的个体中，幼稚表型 T 细胞更加丰富，总 T 细胞的半衰期也延长。 T细胞动力学的这种患者间差异可能反映了HIV-1疾病治疗后功能性免疫重建的差异。
HIV-1 disease is associated with pathological effects on T-cell production, destruction, and distribution. Using the deuterated (2H) glucose method for endogenous labeling, we have analyzed host factors that influence T-cell turnover in HIV-1-uninfected and -infected humans. In untreated HIV-1 disease, the average half life of circulating T cells was diminished without compensatory increases in cell production. Within 12 weeks of the initiation of highly active antiretroviral therapy (HAART), the absolute production rates of circulating T cells increased, and normal half-lives and production rates were restored by 12-36 months. Interpatient heterogeneity in the absolute degree of turnover correlated with the relative proportion of naive- and memory/effector-phenotype T cells in each of the CD4+ and CD8+ populations. The half-lives of naive-phenotype T cells ranged from 116-365 days (fractional replacement rates of 0.19-0.60% per day), whereas memory/effector-phenotype T cells persisted with half-lives from 22-79 days (fractional replacement rates of 0.87-3.14% per day). Naive-phenotype T cells were more abundant, and the half-life of total T cells mas prolonged in individuals with abundant thymic tissue, as assessed by computed tomography. Such interpatient variation in T-cell kinetics may be reflective of differences in functional immune reconstitution after treatment for HIV-1 disease.